Rickets is the term for the end-stage condition in infants and children that begins with suboptimal bone mineralization at the growth plate and progresses with associated physiological perturbations that include secondary hyperparathyroidism, hypocalcemia, and hypophosphatemia leading to irreversible changes in skeletal structure. The disease is a disorder of the growth apparatus of bone in which growth cartilage fails to mature and mineralize normally. Because the bone is undermineralized it is also soft and ductile, and this leads to bowing of the limbs, widening and compression of the ends of the long bones, etc.
In rickets, during prolonged deficiency of calcium (and phosphate), the body increases PTH to prevent hypocalcemia by causing osteoclastic absorption of the bone. This, in turn, causes the bone to become progressively weaker, resulting in rapid osteoblastic activity. The osteoblasts produce large amounts of organic bone matrix, osteoid, which does not become calcified (Guyton and Hall, 2001). Consequently, the newly formed, uncalcified osteoid gradually takes the place of other bone that is being reabsorbed.
During the later stages of rickets, the serum calcium level falls precipitously, and tetany (neuromuscular spasm) develops. In infants and young children, a long-standing calcium intake deficiency, in association with suboptimal vitamin D exposure, can produce rickets. Indeed, in experimental animals and in humans with extremely low vitamin D levels, genetic absence of calcitriol (vitamin D–dependent rickets [VDDR] type I), or genetic absence of the vitamin D receptor (VDDR type II), the use of increased calcium supplementation or calcium infusions will prevent and treat rickets.
These observations indicate that the primary cause of rickets is inadequate delivery of calcium to the bone surface, not a defect in osteoblast function. In other words, the primary role for vitamin D and calcitriol in regulating skeletal homeostasis is indirectly accomplished by stimulating the intestinal absorption of calcium and phosphorus. Nutritional rickets (NR) is still the most common form of growing bone disease despite the efforts of health care providers to reduce the incidence of the disease. Today, it is well known that the etiology of NR ranges from isolated vitamin D deficiency (VDD) to isolated calcium deficiency.
In Turkey, almost all NR cases result from VDD. Recent evidence suggests that in addition to its short- or long-term effects on skeletal development, VDD during infancy may predispose the patient to diseases such as diabetes mellitus, cancer and multiple sclerosis. Among the factors responsible for the high prevalence of VDD in developing countries and its resurgence in developed countries is limited sunshine exposure due to individuals’ spending more time indoors (watching television and working on computer) or avoiding sun exposure intentionally for fear of skin cancer.
Traditional clothing (covering the entire body except the face and hands) further limits the exposure time to sunlight and, thus, decreases the endogenous synthesis of vitamin D. In Turkey, maternal VDD and exclusive breastfeeding without supplementation were reported to be the most prominent reasons leading to NR. The diagnosis of NR is established by a thorough history and physical examination and confirmed by laboratory evaluation.
Recent reports draw attention to the supplemental doses of vitamin D required to achieve a serum 25-hydroxyvitamin D level of at least 20 ng/ml (50 nmol/l) – the serum concentration that is needed to optimize absorption of dietary calcium and to suppress excessive secretion of parathyroid hormone. This type of prevention will also reduce fracture risk as well as prevent long-term negative effect of vitamin D insufficiency. Conflict of interest:None declared. Vitamin D has an essential role in calcium metabolism and bone health.
Vitamin D3 or cholecalciferol is synthesized from 7-dehydrocholesterol or provitamin D3, by sunlight ultraviolet radiation to the skin. 7-dehydrocholesterol is subsequently hydroxylated in the liver and then in the kidney to produce 1,25-(OH)2D3, the active metabolite that binds to specific receptors (VDR) in target tissues, mainly bone and intestine. Other tissues, such as the immune and cardiovascular system, have also VDR. Vitamin D deficiency can induce rickets in children and osteomalacia and osteoporosis in adults.
A possible inverse association between vitamin D levels and the prevalence of metabolic syndrome has been proposed. Vitamin D deficiency increases the risk of type 1 diabetes, insulin resistance, and hypertension, key components of this syndrome. However, other studies have not confirmed this association. Further clinical and experimental studies are needed to ascertain the role of vitamin D in metabolic syndrome Vitamin D deficiency rickets (VDDR) is a disorder biochemically characterized by levated serum alkaline phosphatase (ALP) activity, normal or decreased serum calcium (Ca) and inorganic phosphate concentrations, secondary hyperparathyroidism and decreased serum 25-hydroxyvitamin D (25(OH)D) levels. In stage 1 VDDR, urinary amino acid and phosphate excretion are normal with minimal or no findings of rickets on radiographs. Pseudohypoparathyroidism (PHP) is an inherited disorder characterized by end-organ resistance to parathormone (PTH). VDDR occasionally resembles PHP type 2 in clinical presentation and biochemical features, creating difficulties in the differential diagnosis of these two entities.
Here we report an infant diagnosed with VDDR. In addition to inadequate vitamin D intake, usage of antiepileptic drugs (AED) may have led to the worsening of the vitamin D deficiency. The patient presented with a history of febrile convulsions, for which he received phenobarbital treatment. The initial findings of hypocalcemia, hyperphosphatemia and normal tubular reabsorption of phosphate, mimicking PHP 2, responded well to vitamin D and oral Ca treatment with normalization of serum Ca, phosphorus (P), ALP and PTH levelsConflict of interest:None declared.